Summary
Descripción general del contenido del recurso.
These studies were designed to elucidate the role of NPY in modulating the responses of mPFC to acute stress in mice. Fiberoptic photometry recorded a robust increase in the NPY fluorescent signal in the mPFC during exploration of the elevated O-maze (EOM). An application of a single air puff (stressor) increased anxiety-like behavior and was associated with a decreased NPY signal in the mPFC. Antagonism of Y1 receptors (Y1r) in the mPFC with BIBO3304 decreased time spent in the open compartments of the EOM, identifying a role for endogenous NPY in modulating anxiety-like behavior. While the chemogenetic actuation of local parvalbumin neurons (PVs) increased anxiety-like behavior, an injection of NPY into the mPFC decreased the Ca2+ signal detected from PVs in response to the stressor, an indication of NPY-mediated inhibition of PVs. Injection of NPY into the mPFC increased, while injection of BIBO3304 decreased, the Ca2+ signal detected from mPFC→BLA projections in response to the air puff stress. Viral tracing demonstrated that, while NPY neurons in the mPFC receive monosynaptic input from many brain regions, their axonal output is restricted to layers of the mPFC, with one of the targets being local PVs. These results demonstrate that ongoing inhibition of PV activity in the mPFC by NPY via Y1r influences anxiety-like activity in mice, likely through strengthening mPFC output to the BLA. Subjecting animals to an acute stress disrupts this circuitry, providing further and new support for a role of NPY in the mPFC and the modulation of stress-related behaviors. These studies were designed to elucidate the role of NPY in modulating the responses of mPFC microcircuitry to acute stress in mice. Using an NPY biosensor in the mPFC, fiberoptic photometry recorded a robust increase in the NPY fluorescent signal during exploration of the elevated O-maze (EOM). An application of a single air puff (stressor) increased anxiety-like behavior in the EOM and was associated with a decreased NPY signal in the mPFC, supporting a possible link between NPY signaling and levels of anxiety. Antagonism of Y1 receptors (Y1r) in the mPFC with BIBO3304 decreased time spent in the open compartments of the EOM, identifying a role for endogenous NPY in modulating anxiety-like behavior. The chemogenetic actuation of local parvalbumin neurons (PVs) increased anxiety-like behavior. Conversely, an injection of NPY into the mPFC decreased the Ca2+ signal detected from PVs in response to the stressor, an indication of NPY-mediated inhibition of PVs. Injection of NPY into the mPFC significantly increased, while injection of BIBO3304 decreased, the Ca2+ signal detected from mPFC→BLA projections in response to the air puff stress. Viral tracing demonstrated that, while NPY neurons in the mPFC receive monosynaptic input from many brain regions, their axonal output is restricted to layers of the mPFC, with one of the targets being local PVs. These results demonstrate that ongoing inhibition of PV activity in the mPFC by NPY via Y1r influences anxiety-like activity in mice, likely through strengthening mPFC output to the BLA. Subjecting animals to an aversive air puff acute stress disrupts this circuitry, providing further and new support for a role of NPY in the mPFC and the modulation of stress-related behaviors.
